Acetic Acid → 1-methyl-1H-pyrrolo(2,3-c)pyridine-2-carboxylic acid

HRID 217170Notes

Reaction equation

HRID 217170 reaction equation
C([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:9]2=[CH:10][N:11]=[CH:12][CH:13]=[C:8]2[CH:7]=1)=[O:5])C.[OH-].[Na+].CC(O)=O>CCO>[CH3:15][N:14]1[C:9]2=[CH:10][N:11]=[CH:12][CH:13]=[C:8]2[CH:7]=[C:6]1[C:4]([OH:5])=[O:3]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 58117018ethyl 1-methyl-1H-pyrrolo[2,3-c]pyridine-2-carboxylate

Product 1

HCID 576594781-methyl-1H-pyrrolo(2,3-c)pyridine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

NaH (60% dispersion in mineral oil, 51 mg, 1.26 mmol) was added to a solution of 1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester (200 mg, 1.05 mmol) in anhydrous DMF (10 mL) at 0° C. The mixture was stirred for 1 h, before being treated with MeI (79 μL, 1.26 mmol) and allowed to warm to 20° C. After 16 h, saturated aqueous NH4Cl (10 mL) was added, then the suspension was stirred vigorously for 1 h. The mixture was partitioned between H2O (10 mL) and EtOAc (30 mL), then the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine (20 mL), dried (MgSO4), filtered, and concentrated, then the residue was purified by flash chromatography (IH-EtOAc, 1:1) to provide 1-methyl-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid ethyl ester: δH (CDCl3): 1.45 (t, 3H), 4.20 (s, 3H), 4.42 (q, 2H), 7.25 (s, 1H), 7.58 (d, 1H), 8.36 (d, 1H), 8.95 (s, 1H). A solution of this ester (36 mg, 180 μmol) in EtOH (3 mL) was treated with 2 M NaOH (270 μL, 540 μmol), then the mixture was stirred at 60° C. for 4 h. On cooling to ambient temperature, the mixture was treated dropwise with dilute AcOH to adjust the pH to 4. The resulting suspension was allowed to stand at ambient temperature for 7 d, then the precipitated solid was collected, washed with H2O, and dried to furnish the title compound: δH(CD3OD): 4.23 (s, 3H), 7.20 (s, 1H), 8.01 (d, 1H), 8.17 (d, 1H), 9.12 (s, 1H).

Workup

  1. temperatureOn cooling to ambient temperature
  2. waitto stand at ambient temperature for 7 d
  3. customthe precipitated solid was collected
  4. washwashed with H2O
  5. customdried

Sources & evidence

ORD record
ord-070fd9747e3a475dac271326373e2b43
Source dataset
uspto-grants-2012_06
Patent number
US08193359B2

Reaction notes

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